GREEN TECHNIQUES FOR ORGANIC SYNTHESIS AND MEDICINAL CHEMISTRY -- Contents -- List of Contributors -- Foreword -- Preface -- PART I: INTRODUCTION -- 1 Green Toxicology -- 1.1 Introduction -- 1.2 History and Scope of Toxicology -- 1.2.1 The need for green toxicology -- 1.3 Principles of Toxicology -- 1.3.1 Characteristics of exposure -- 1.3.2 Spectrum of toxic effects -- 1.3.3 The dose-response relationship -- 1.4 Disposition of Toxicants in Organisms -- 1.4.1 Absorption -- 1.4.2 Distribution -- 1.4.3 Metabolism -- 1.4.4 Excretion -- 1.5 Non-Organ System Toxicity -- 1.5.1 Carcinogenesis -- 1.5.2 Reproductive and developmental toxicity -- 1.5.3 Immunotoxicology -- 1.6 Mechanistic Toxicology -- 1.7 Quantitative Structure-Activity Relationships -- 1.8 Environmental Toxicology -- 1.8.1 Persistence and bioaccumulation -- 1.9 Risk Assessment -- 1.9.1 Non-Cancer risk assessment -- 1.9.2 Cancer risk assessment -- 1.10 Conclusions -- References -- 2 Green Chemistry and the Pharmaceutical Industry -- 2.1 Introduction -- 2.2 Green Chemistry versus Sustainable Chemistry -- 2.3 Trend: The Ongoing Use of Hazardous Chemistry -- 2.4 Myth: To Do Green Chemistry One Must Sacrifice Performance and Cost -- 2.5 Green Chemistry and the Future of the Pharmaceutical Industry -- 2.6 Green Chemistry in Pharmaceutical Process Development and Manufacturing -- 2.7 Conclusions -- References -- 3 Environmental Science -- Guiding Green Chemistry, Manufacturing, and Product Innovations -- 3.1 Introduction -- 3.2 Market Forces -- 3.2.1 Chemicals in the natural and human environment -- 3.2.2 Precautionary decision making -- 3.2.3 Chemical control laws -- 3.2.4 Green chemistry initiatives -- 3.2.5 Drug registration Environmental Risk Assessment (ERA) -- 3.2.6 Extended Producer Responsibility (EPR) -- 3.2.7 Ecosystem valuation -- 3.2.8 Company expectations.

3.2.9 Public expectations -- 3.2.10 Environmental labeling, standards, and classification -- 3.3 Indicators (Attributes) of Environmental Performance -- 3.4 Environmental Impact -- 3.5 Strategic Approach to Greener Manufacturing Processes and Products -- 3.6 Manufacturing Process Improvements -- 3.6.1 Business and Professional Advantages from Manufacturing Process Improvements -- 3.7 Product Improvements -- 3.8 Environmental Decision Making -- 3.8.1 E-factor -- 3.8.2 Process Mass Intensity (PMI) -- 3.8.3 Life Cycle Assessment (LCA) -- 3.8.4 Individual company initiatives -- 3.8.5 Environmental (Ecological) Risk Assessment (ERA) -- 3.8.6 Alternatives Assessment (AA)/Chemical Alternatives Assessment (CAA) -- 3.8.7 Green Screen -- 3.8.8 iSUSTAIN™ green chemistry index -- 3.8.9 Computational science and Quantitative Structure-Activity Relationships (QSARs) -- 3.8.10 Tiered testing -- 3.8.11 Databases and lists of chemicals -- 3.9 Case Study - Pharmaceuticals/Biologics -- 3.9.1 Pharmaceutical manufacturing -- 3.9.2 Pharmaceutical products -- 3.10 Case Study - Nanotechnology -- 3.11 Green Credentials and Environmental Standards -- 3.12 Inspiring Innovation - Academic and Industry Programs -- 3.12.1 Academic programs -- 3.12.2 Industry programs -- 3.13 Conclusions and Recommendations -- References -- PART II: GREEN CATALYSIS -- 4 Catalytic C―H Bond Activation Reactions -- 4.1 Introduction -- 4.2 Homogeneous C―H Activation by Metal Complex Catalysis -- 4.2.1 Pd-catalyzed carbon-carbon bond formations -- 4.2.2 Pd-catalyzed carbon-heteroatom bond formation -- 4.2.3 C―H activation by other metals -- 4.3 Heterogeneous Catalytic Methods for C―H Activation -- 4.3.1 Supported metal complexes -- 4.3.2 Supported metals -- 4.4 C―H Activation by Organocatalysts -- 4.5 Enzymatic C―H Activations -- References -- 5 Supported Asymmetric Organocatalysis -- 5.1 Introduction.

5.2 Polymer-Supported Organocatalysts -- 5.2.1 Polymer-supported chiral amines for enamine and iminiun catalysis -- 5.2.2 Polymer-supported phase transfer catalysts -- 5.2.3 Polymer-supported phosphoric acid catalyst -- 5.2.4 Miscellaneous -- 5.3 Solid Acid-Supported Organocatalysis -- 5.3.1 Polyoxometalate-supported chiral amine catalysts -- 5.3.2 Solid sulfonic acid supported chiral amine catalysts -- 5.4 Ionic Liquid-Supported Organocatalysts -- 5.5 Magnetic Nanoparticle-Supported Organocatalysts -- 5.6 Silica-Supported Asymmetric Organocatalysts -- 5.6.1 Silica-supported proline and its derivatives -- 5.6.2 Silica-supported MacMillan catalysts -- 5.6.3 Other silica-supported organocatalysts -- 5.7 Clay Entrapped Organocatalysts -- 5.8 Miscellaneous -- 5.9 Conclusion -- Acknowledgments -- References -- 6 Fluorous Catalysis -- 6.1 Introduction and the Principles of Fluorous Catalysis -- 6.2 Ligands for Fluorous Transition Metal Catalysts -- 6.3 Synthetic Application of Fluorous Catalysis -- 6.3.1 Hydroformylation -- 6.3.2 Hydrogenation -- 6.3.3 Hydrosylilation -- 6.3.4 Cross-coupling reactions -- 6.3.5 Hydroboration -- 6.3.6 Oxidation -- 6.3.7 Esterification, transesterification and acetylation -- 6.3.8 Other metal catalyzed carbon-carbon bond forming reactions -- 6.4 Fluorous Organocatalysis -- References -- 7 Solid-Supported Catalysis -- 7.1 Introduction -- 7.1.1 General Introduction -- 7.1.2 The impact of solid-phase organic synthesis on green chemistry -- 7.2 Immobilized Palladium Catalysts for Green Chemistry -- 7.2.1 Introduction -- 7.2.2 Suzuki reactions -- 7.2.3 Heck-Mizoroki reactions in water -- 7.2.4 Sonogashira reactions in water -- 7.2.5 Tsuji-Trost reactions in water -- 7.3 Immobilized Rhodium Catalysts for Green Chemistry -- 7.3.1 Introduction -- 7.3.2 Rhodium(II) carbenoid chemistry.

7.3.3 Rhodium (I)-catalyzed conjugate addition reactions -- 7.3.4 Rhodium-catalyzed hydrogenation reactions -- 7.3.5 Rhodium-catalyzed carbonylation reactions -- 7.4 Immobilized Ruthenium Catalysts for Green Chemistry -- 7.4.1 Introduction -- 7.4.2 Ruthenium-catalyzed metathesis reactions -- 7.4.3 Ruthenium-catalyzed transfer hydrogenation -- 7.4.4 Ruthenium-catalyzed opening of epoxides -- 7.4.5 Ruthenium-catalyzed cyclopropanation reactions -- 7.4.6 Ruthenium-catalyzed halogenation reactions -- 7.5 Other Immobilized Catalysts for Green Chemistry -- 7.5.1 Immobilized cobalt catalysts -- 7.5.2 Immobilized copper catalysts -- 7.5.3 Immobilized iridium catalysts -- 7.6 Conclusions -- References -- 8 Biocatalysis -- 8.1 Introduction -- 8.2 Brief History of Biocatalysis -- 8.3 Biocatalysis Toolboxes -- 8.4 Enzymatic Synthesis of Pharmaceuticals -- 8.4.1 Synthesis of atorvastatin and rosuvastatin -- 8.4.2 Synthesis of β-lactam antibiotics -- 8.4.3 Synthesis of glycopeptides -- 8.4.4 Synthesis of tyrocidine antibiotics -- 8.4.5 Synthesis of polyketides -- 8.4.6 Synthesis of taxoids and epothilones -- 8.4.7 Synthesis of pregabalin -- 8.5 Summary -- Acknowledgment -- References -- PART III: GREEN SYNTHETIC TECHNIQUES -- 9 Green Solvents -- 9.1 Introduction -- 9.2 Origins of the Neoteric Solvents -- 9.2.1 Ionic liquids -- 9.2.2 Supercritical carbon dioxide -- 9.2.3 Water -- 9.2.4 Perfluorinated solvents -- 9.2.5 Biosolvents -- 9.2.6 Petroleum solvents -- 9.3 Application of Green Solvents -- 9.3.1 Synthetic organic chemistry overview -- 9.3.2 Diels-Alder cycloaddition -- 9.3.3 Cross-coupling -- 9.3.4 Ring-closing metathesis -- 9.4 Recapitulation and Possible Future Developments -- References -- 10 Organic Synthesis in Water -- 10.1 Introduction -- 10.2 Pericyclic Reactions -- 10.3 Passerini and Ugi Reactions -- 10.4 Nucleophilic Ring-Opening Reactions.

10.5 Transition Metal Catalyzed Reactions -- 10.5.1 Pericyclic reactions -- 10.5.2 Addition reactions -- 10.5.3 Coupling reactions -- 10.5.4 Transition metal catalyzed reactions of carbenes -- 10.5.5 Oxidations and reductions -- 10.6 Organocatalytic Reactions -- 10.6.1 Aldol reaction -- 10.6.2 Michael addition -- 10.6.3 Mannich reaction -- 10.6.4 Cycloaddition reactions -- 10.7 Miscellaneous -- 10.8 Conclusion -- References -- 11 Solvent-Free Synthesis -- 11.1 Introduction -- 11.2 Alternative Methods to Solution Based Synthesis -- 11.2.1 Mortar and pestle -- 11.2.2 Ball milling -- 11.2.3 Microwave assisted solvent-free synthesis -- References -- 12 Microwave Synthesis -- 12.1 Introduction -- 12.2 The Mechanism of Microwave Heating -- 12.3 The Green Properties of Microwave Heating -- 12.3.1 Green solvents -- 12.3.2 Energy reduction -- 12.3.3 Improved reaction outcomes resulting in less purification -- 12.4 Microwaves versus Green Chemistry Principles -- 12.5 Green Solvents in Microwave Chemistry -- 12.5.1 Water -- 12.5.2 Solventless reactions -- 12.5.3 Ionic liquids -- 12.5.4 Glycerol -- 12.6 Catalysis -- 12.6.1 Microwave assisted C―H bond activation -- 12.6.2 Microwave assisted carbonylation reactions -- 12.7 Microwave Chemistry Scale-Up -- 12.7.1 Flow microwave reactors -- 12.7.2 Energy efficiency of large-scale microwave reactions -- 12.7.3 Large-scale batch microwave reactors -- 12.7.4 Future work in microwave scale-up -- 12.8 Summary -- References -- 13 Ultrasonic Reactions -- 13.1 Introduction -- 13.2 How Does Cavitation Work? -- 13.3 Condensation Reactions -- 13.4 Michael Additions -- 13.5 Mannich Reactions -- 13.6 Heterocycles Synthesis -- 13.7 Coupling Reactions -- 13.8 Miscellaneous -- 13.9 Conclusions -- References -- 14 Photochemical Synthesis -- 14.1 Introduction -- 14.2 Synthesis and Rearrangement of Open-Chain Compounds.

14.3 Synthesis of Three- and Four-Membered Rings.